Joint pain

WHAT SHOULD WE KNOW ABOUT JOINTS?
The bones of the human skeletal system are connected by a complex series of joints, which connect two or more bones and allow for a wide variety of movements that would otherwise be impossible (Briant 2008).

In order to facilitate smooth joint movement, the surfaces of joints are lined by a low-friction, load-distributing, wear-resistant tissue called articular cartilage, which is composed of 65 to 80 percent water, collagen (fibrous proteins), proteoglycans, and chondrocytes (cells that produce cartilage) (Pearle 2005). 

In adults, damaged cartilage has a very limited capacity for self-healing due to blood supply limitations, and the relatively poor capacity of resident chondrocytes to migrate and proliferate (Henrotin 2009).

JOINT PAIN
Joints provide support and help us move. Any damage to the joints from disease or injury can interfere with our movement and cause a lot of pain (Zelman 2017).

Joint pain is extremely common. In one survey in the US, about one-third of adults reported having joint pain within the past 30 days. Knee pain was the most common complaint, followed by shoulder and hip pain, but joint pain can affect any part of our body, from ankles and feet to shoulders and hands. As we get older, painful joints become increasingly more common (Zelman 2017).

Joint pain can range from mildly irritating to debilitating. It may go away after a few weeks (acute), or last for several weeks or months (chronic). Even short-term pain and swelling in the joints can affect our quality of life (Zelman 2017).

Many different conditions can lead to painful joints, including osteoarthritis, rheumatoid arthritis, bursitis, gout, strains, sprains, and other injuries (Zelman 2017).

OSTEOARTHRITIS - DEFINITION
Osteoarthritis (OA), also called a degenerative joint disease, is the clinical and pathological outcome of a range of disorders that result in structural and functional failure of synovial joints. It is primarily a disease of the cartilage that ultimately leads to a local tissue response, usually consisting of inflammation, and consequently to mechanical changes that culminate in the failure of these structures to function normally; therefore, the entire joint organ, including the subchondral bone, menisci, ligaments, periarticular muscle, capsule, and synovium is involved in the pathological process (Sakalauskienė 2010).

Osteoarthritis is the most common musculoskeletal disease worldwide and leads to functional decline and loss in quality of life (Pereira 2015).

OSTEOARTHRITIS - EPIDEMIOLOGY
OA typically becomes symptomatic later in life, usually after the age of 50, though it may start earlier, such as when joint injury has occurred or in familial forms. It is the most common form of arthritis worldwide, affecting an estimated 250 million people; about 80% of people over 65 having radiographic evidence of OA (American College of Rheumatology (ACR) 2017).

OA most frequently affects the joints of the knees, hands, hips, and spine, and is a leading musculoskeletal cause of impaired mobility in the elderly (Xia 2014).


OSTEOARTHRITIS – ETIOLOGY AND RISK FACTORS
The etiology of OA is multi-factorial, including genetic predisposition, aging, obesity, joint mal-alignment and prior joint injury or surgery (Xia 2014).

Several risk factors can increase the likelihood of OA. Women are more likely to develop OA than men. Obesity may increase the risk through physical stress on joints. Occupations in which excessive joint loading occurs (e.g. athletes, jobs involving frequent squatting, heavy lifting), and repeated microtrauma or overt joint injury are also major risk factors (American College of Rheumatology (ACR) 2017).


OSTEOARTHRITIS – CLINICAL MANIFESTATION
The major clinical symptoms of OA include chronic pain, joint instability, stiffness, joint deformities, and radiographic joint space narrowing (Xia 2014).

The pain in osteoarthritis is frequently activity-related; constant pain frequently becomes a feature later in the disease. However, pain is not the only consequence of osteoarthritis experienced by patients. Pain is linked with function, with physical movements triggering pain, while pain, in turn, causes limitations in physical function. Joint stiffness particularly in the morning is also frequent; sensation of instability or buckling and also an audible and palpable ‘cracking’ or ‘crunching’ over a joint during its active or passive movement are also common especially in later stages. Functional disability is another key element in osteoarthritis. Osteoarthritis causes changes in mobility and function - patients frequently experience physical limitations, difficulties with personal care, work ability and even problems with maintaining their households (Pereira 2015).

OSTEOARTHRITIS - TREATMENT
The major goals of treatment are pain control with minimal adverse effects, stiffness reduction, maintenance or improvement of joint mobility and function, and improved health related quality of life (Pereira 2015; Xia 2014). Treatment should be tailored to each individual. Because no single therapy is adequate, the major clinical guidelines for disease management generally agree that therapy should involve a combination of non-pharmacologic and pharmacologic therapies (Pereira 2015).

Non-pharmacologic therapies for osteoarthritis are quite diverse but broadly divided into educational and physical approaches. Educational approaches are based on lifestyle pattern changes (including diet and exercise), joint protection techniques and walking aids. Physical exercises include aerobic activity, muscle strengthening and range-of-motion exercises (Pereira 2015).

Physiotherapy strategies such as electrotherapy, thermal and manual therapy are also recommended depending on the individual patient (Pereira 2015).

Surgical procedures are advised in patients with a long lasting disease and/or pain or disability which are poorly controlled with non-surgical methods; surgical options include lavage/debridement, corrective osteotomy and arthroplasty (Pereira 2015).

Pharmacologic therapies recommended for the initial management of patients with osteoarthritis include various medications and nutritional supplements: 

  • Medications - acetaminophen (paracetamol), oral and topical non-steroidal anti-inflammatory drugs (NSAIDs, e.g. naproxen and ibuprofen), tramadol, and intra-articular corticosteroid injections. Intra-articular hyaluronate injections, duloxetine and opioids are conditionally recommended in patients with an inadequate response to initial therapy (Pereira 2015).
  • Nutritional supplements - glucosamine, chondroitin sulphate, methylsulfonylmethane, Boswellia serrata, avocado and soybean unsaponifiables (ASU), hyaluronic acid, collagen type II (Pereira 2015).

Non-steroidal anti-inflammatory drugs. Among pharmacological treatments, NSAIDs, including cyclo-oxygenase 2 (COX-2) inhibitors, despite the serious side effects associated with their long-term use, remain the most widely prescribed drugs for OA (Ameye and Chee 2006).  Because of the high incidence of adverse events associated with NSAID therapy, effective and safe alternative treatments for the management of OA pain are highly desirable (Vishal 2011). Such preventive and curative alternatives could come from nutrition (Ameye and Chee 2006).
OA as a chronic disease is the perfect paradigm of a pathology the treatment of which could be addressed by nutrition. By nature, nutrition is better positioned to provide long-term rather than short-term health benefits (Ameye and Chee 2006).
Natural products can be safer than prescription medications with less undesirable side effects. They are used to treat mild to moderate pain and to alleviate symptoms thus aiming at reducing the consumption of NSAIDs (Christiansen 2015).
Some nutritional ingredients have been scientifically researched and have well documented data on their mechanisms of action and efficacy in conditions like OA:

Joint building support
Glucosamine Sulphate. Glucosamine is a natural constituent of glycosaminoglycans in the cartilage matrix and synovial fluid, which when administered exogenously, exerts pharmacological effects on osteoarthritic cartilage and chondrocytes. The symptomatic as well as disease-modifying effects attributed to glucosamine sulphate may be based upon reports of downregulation in the expression of several inflammatory and degenerative mediators resulting in attenuation of degradation of the cartilage with reduction of disease progression (O. Bruyère 2016). Glucosamine sulfate at the oral once-daily dosage of 1,500 mg is more effective than placebo in treating knee OA symptoms (Herrero-Beaumont 2007). Glucosamine delays progression on knee osteoarthritis measured by changes in radiographic minimum joint space width (Pavelka 2002). The long-term combined structure-modifying and symptom-modifying effects of glucosamine sulphate suggest that it could be a disease modifying agent in osteoarthritis (Reginster 2001).
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Hyaluronic acid (HA) is a mucopolysaccharide comprised of tandem repeats of D-glucuronic acid and N-acetyl glucosamine. It is abundantly present in the synovial fluid and cartilage (Tashiro 2012; Bowman 2018). Synovial fluid has the highest concentration of HA anywhere in the body at 3–4 mg/mL. The viscosity of synovial fluid is attributable to HA and serves as a lubricant for joint movements (Oe 2016). The functions of HA in the joint include lubrication, serving as a space filler to allow the joint to stay open, and the regulation of cellular activities such as binding of proteins (Bowman 2018). Its effectiveness in OA is due to the many actions it deploys, including lubrication, anti-inflammatory and chondroprotective effects (Bowman 2018). The efficacy of oral HA in relieving knee pain in OA patients was demonstrated in several clinical trials (Oe 2016).

Boron is an essential nutrient for healthy bones and joints. Evidence suggests that it is safe and effective for the treatment of OA (Newnham 1994). Published clinical research has suggested that boron has the ability to improve symptoms associated with inflammatory conditions, such as joint discomfort and osteoarthritis (Pietrzkowski 2014). It has shown significant improvement in knee discomfort and function over a period of 2 weeks (Pietrzkowski 2014). Boron also reduces the risk of exaggerated inflammatory disease (Hunt 1999).

Chondroitin sulphate is a heterogeneous polysaccharide molecule (Martel-Pelletier 2015). Chondroitin sulfate occurs naturally in the extracellular matrix of connective tissues, e.g., bone, cartilage, skin, ligaments and tendons (Tat 2007). Chondroitin sulfate has been shown to elicit a range of beneficial effects: anti-inflammatory effects, an increase in type II collagen and proteoglycans, a reduction in bone resorption and a better anabolic/catabolic balance in chondrocytes (Tat 2007; Hochberg 2013; Monfort 2008).

Joint flexibility support
Avocado/soybean unsaponifiables (ASU) are made of unsaponifiable fractions of one­third avocado oil and two-thirds soybean oil (Maheu 1998).The intake of avocado-soybean unsaponifiables is recommended by the American College of Rheumatology (ACR) and the European League against Rheumatism (EULAR) (Osteoarthritis and Cartilage (2008).ASU possesses chondroprotective, anabolic, and anticatabolic properties as well as anti-inflammatory properties. It inhibits the breakdown of cartilage and promotes cartilage repair by inhibiting a number of molecules and pathways implicated in OA. ASU stimulates the synthesis of collagen and aggrecan by inhibiting inflammatory cytokines. At the clinical level, ASU reduces pain and stiffness while improving joint function (Christiansen 2015). In the study by Blotman et al., ASU significantly reduced the consumption of nonsteroidal anti-inflammatory drugs (NSAIDs) and delayed the resumption of NSAIDs after they had been stopped in patients with symptomatic knee or hip OA who had regularly taken NSAIDs. The effects unfolded from 1-2 months of ASU treatment (Maheu 1998). ASU treatment showed significant symptomatic efficacy over placebo in the treatment of OA (Maheu 1998). ASU significantly reduced the progression of joint space loss as compared with placebo in the subgroup of patients with advanced joint space narrowing (Lequesne 2002).

Undenatured Collagen Type II (UC-II). Collagen type II is the main structural element of the cartilage, tendons and ligaments (Bakilan 2016). UC-II is a novel undenatured type II collagen derived from chicken sternum cartilage (Crowley 2009). Orally taken native type II collagen antigens interact with Peyer’s patches in the gut associated lymphoid tissue, resulting in turning off the T-cell attack to the structural protein collagen type II in the cartilage. This desensitization process in Peyer’s patch, also known as oral tolerance, avoids the recognition of endogenous collagen type II in the cartilage as antigen by the immune system. Considering this mechanism of action, native type II collagen may have positive effects on inflammation and degradation in joint diseases (Bakilan 2016). Treatment with UC-II reduced WOMAC, VAS and Lequesne's functional index statistically more significantly than Glucosamine and Chondroitin combination. UC-II supplementation showed improvement in daily activities suggesting an improvement in overall quality of life in the patients receiving UC-II (Crowley 2009).


Joint comfort support
Cissus quadrangularis extract exhibits significant analgesic activity compared to that of acetylsalicylic acid when tested using Haffner’s clip and Eddy’s hot plate methods (Garima Mishra 2010). The analgesic effect is of great value in relief of pain which is a constant feature in OA. In addition to its analgesic activity Cissus quadrangularis also possesses anti-inflammatory activity by inhibiting cyclooxygenase and lipoxygenase pathways of arachidonic acid metabolism (Garima Mishra 2010). In a pilot study with young, otherwise healthy, exercise-trained men with joint-specific pain, supplementation with Cissus quadrangularis reduced joint pain (Bloomer 2013).

Boswellia serrata extract contains boswellic acids. Acetyl-11-keto-beta-boswellic acid is the most active compound of Boswellia extract and is a potent inhibitor of 5-lipoxygenase, a key enzyme in the cellular inflammatory cascade (Sengupta 2010). A number of independent clinical studies support the anti-inflammatory and anti-arthritic properties of Boswellia extract. Available data demonstrate its efficacy in pain management, improving physical function, quality of life and joint health. In addition to its efficacy, Boswellia extract is safe as no major adverse events were reported even for long-term supplementation (Sengupta 2010).

S-Adenosylmethionine (SAMe). SAMe is an important physiologic compound that is distributed throughout the body tissues and fluids. It is produced endogenously from methionine and adenosine triphosphate (ATP). It is an important methyl group donor playing an essential role in many biochemical reactions involving enzymatic transmethylation (Friedel 1989). Clinical trials have shown that SAMe can reduce pain, stiffness, and increase functioning among patients with OA (Hardy 2003; Kim 2009).

Omega-6 (n-6) polyunsaturated fatty acid (PUFA). PUFAs are essential fatty acids and precursors to a number of important factors called eicosanoids, such as prostaglandins, thromboxanes, leukotrienes and resolvins. These mediate various processes including inflammation and bone metabolism. Conversion of PUFAs to eicosanoids is achieved by the action of cyclo-oxygenases (COX) and lipoxygenases (LOX). Omega-3 and n-6 generate different series of eicosanoids, those from n-6 are generally highly pro-inflammatory and those from n-3 somewhat less so. In particular, PGE2, derived from n-6 PUFAs, has been associated with inhibition of anabolic processes and increased proteolytic degradation of cartilage (Heinecke 2010; Li 2009; Attur 2008).


HIGHLIGHTS

  • Osteoarthritis (OA) is a degenerative joint disease that frequently affects the hands and weight bearing joints of the body (Bowman 2018).
  • OA is the most common form of arthritis. Nowadays OA is one of the most frequent chronic diseases and, with the increase in life expectancy, both its incidence and prevalence are expected to rise. This condition is progressive and leads to functional decline and loss in quality of life, with important health care and society costs (Pereira 2015).
  • The patients with OA are suffering from persistent pain, stiffness and limited mobility. The disease also directly affects their quality of life with physical and/or mental co-morbidity (Bowman 2018).
  • The management of OA is largely palliative, focusing on the alleviation of symptoms. Current recommendations for the management of OA include a combination of non-pharmacological interventions and pharmacological treatments. Among pharmacological treatments, NSAIDs, despite serious adverse effects associated with their long-term use, remain the most widely prescribed drugs for OA (Ameye and Chee 2006).
  • There is a need for safe and effective alternatives for OA that could come from nutritional supplements. Scientific evidence exists for some specific natural treatments to provide symptom relief to osteoarthritic patients (Ameye and Chee 2006).

Reference

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